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Neonatal jaundice

Issued: May 2010

NICE clinical guideline 98

guidance.nice.org.uk/cg98

NICE has accredited the process used by the Centre for Clinical Practice at NICE to produce

guidelines. Accreditation is valid for 5 years from September 2009 and applies to guidelines produced

since April 2007 using the processes described in NICE's 'The guidelines manual' (2007, updated

2009). More information on accreditation can be viewed at www.nice.org.uk/accreditation

NICE 2010

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Contents

Introduction ................................................................................................................................. 4

Patient-centred care .................................................................................................................... 6

Key terms used in this guideline .......................................................................................................... 6

Key priorities for implementation ................................................................................................ 8

1 Guidance .................................................................................................................................. 11

1.1 Information for parents or carers..................................................................................................... 12

1.2 Care for all babies .......................................................................................................................... 12

1.3 Management and treatment of hyperbilirubinaemia........................................................................ 15

1.4 Measuring and monitoring bilirubin thresholds during phototherapy .............................................. 16

1.5 Factors that influence the risk of kernicterus .................................................................................. 20

1.6 Formal assessment for underlying disease .................................................................................... 21

1.7 Care of babies with prolonged jaundice ......................................................................................... 21

1.8 Intravenous immunoglobulin .......................................................................................................... 22

1.9 Exchange transfusion ..................................................................................................................... 22

1.10 Other therapies ............................................................................................................................. 23

2 Notes on the scope of the guidance......................................................................................... 25

3 Implementation ........................................................................................................................ 26

4 Research recommendations .................................................................................................... 27

4.1 Breastfeeding and hyperbilirubinaemia........................................................................................... 27

4.2 Trancutaneous bilirubin screening and risk factors ........................................................................ 27

4.3 Transcutaneous bilirubinometers .................................................................................................... 28

4.4 Interruptions during phototherapy .................................................................................................. 28

4.5 National registries .......................................................................................................................... 29

5 Other versions of this guideline ................................................................................................ 30

5.1 Full guideline ................................................................................................................................... 30

Neonatal jaundice NICE clinical guideline 98

NICE 2010. All rights reserved. Last modified May 2010 Page 2 of 41

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5.2 Quick reference guide ..................................................................................................................... 30

5.3 Information for the public................................................................................................................. 30

6 Related NICE guidance............................................................................................................ 31

7 Updating the guideline.............................................................................................................. 32

Appendix A: The Guideline Development Group and acknowledgements.................................. 33

NICE project team................................................................................................................................. 35

Acknowledgements ............................................................................................................................... 35

Appendix B: The Guideline Review Panel................................................................................... 37

Appendix C: The algorithms........................................................................................................ 38

Appendix D: The treatment threshold graphs.............................................................................. 39

About this guideline ..................................................................................................................... 40



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Introduction

Jaundice is one of the most common conditions needing medical attention in newborn babies.

Jaundice refers to the yellow colouration of the skin and the sclerae (whites of the eyes) caused

by the accumulation of bilirubin in the skin and mucous membranes. Jaundice is caused by a

raised level of bilirubin in the body, a condition known as hyperbilirubinaemia.

Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life,

and about 10% of breastfed babies are still jaundiced at 1 month. For most babies, jaundice is

not an indication of an underlying disease, and this early jaundice (termed 'physiological

jaundice') is generally harmless.

Breastfed babies are more likely than bottle-fed babies to develop physiological jaundice within

the first week of life. Prolonged jaundice that is, jaundice persisting beyond the first 14 days

is also seen more commonly in these babies. Prolonged jaundice is generally harmless, but can

be an indication of serious liver disease.

Jaundice has many possible causes, including blood group incompatibility (most commonly

Rhesus or ABO incompatibility), other causes of haemolysis (breaking down of red blood cells),

sepsis (infection), liver disease, bruising and metabolic disorders. Deficiency of a particularenzyme, glucose-6-phosphate-dehydrogenase, can cause severe neonatal jaundice.

Glucose-6-phosphate-dehydrogenase deficiency is more common in certain ethnic groups and

runs in families.

Bilirubin is mainly produced from the breakdown of red blood cells. Red cell breakdown produces

unconjugated (or 'indirect') bilirubin, which circulates mostly bound to albumin although some is

'free' and hence able to enter the brain. Unconjugated bilirubin is metabolised in the liver to

produce conjugated (or 'direct') bilirubin which then passes into the gut and is largely excreted instool. The terms direct and indirect refer to the way the laboratory tests measure the different

forms. Some tests measure total bilirubin and do not distinguish between the two forms.

In young babies, unconjugated bilirubin can penetrate the membrane that lies between the brain

and the blood (the bloodbrain barrier). Unconjugated bilirubin is potentially toxic to neural tissue

(brain and spinal cord). Entry of unconjugated bilirubin into the brain can cause both short-term

and long-term neurological dysfunction (bilirubin encephalopathy). The term kernicterus is used

to denote the clinical features of acute or chronic bilirubin encephalopathy, as well as the yellow



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staining in the brain associated with the former. The risk of kernicterus is increased in babies with

extremely high bilirubin levels. Kernicterus is also known to occur at lower levels of bilirubin in

term babies who have risk factors, and in preterm babies.

Clinical recognition and assessment of jaundice can be difficult. This is particularly so in babies

with darker skin tones. Once jaundice is recognised, there is uncertainty about when to treat, and

there is widespread variation in the use of phototherapy and exchange transfusion. There is a

need for more uniform, evidence-based practice and for consensus-based practice where such

evidence is lacking. This guideline provides guidance regarding the recognition, assessment and

treatment of neonatal jaundice. The advice is based on evidence where this is available and on

consensus-based practice where it is not.

The guideline will assume that prescribers will use a drug's summary of product characteristics to

inform decisions made with individual patients.



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Patient-centred care

This guideline offers best practice advice on the care of babies with neonatal jaundice.

Treatment and care should take into account parents' preferences. Parents of babies with

neonatal jaundice should have the opportunity to make informed decisions about their babies'

care and treatment, in partnership with their healthcare professionals. If parents do not have the

capacity to make decisions, healthcare professionals should follow the Department of Health's

advice on consent and the code of practice that accompanies the Mental Capacity Act. In Wales,

healthcare professionals should follow advice on consent from the Welsh Government.

Healthcare professionals should follow the guidelines in the Department of Health's Seeking

consent: working with children.

Good communication between healthcare professionals and parents is essential. It should be

supported by evidence-based written information tailored to the parent's needs. Treatment and

care, and the information parents are given about it, should be culturally appropriate. It should

also be accessible to people with additional needs such as physical, sensory or learning

disabilities, and to people who do not speak or read English.

Key terms used in this guideline

Conventional phototherapy Phototherapy given using a single light source (not fibreoptic) that

is positioned above the baby

Direct antiglobulin test (DAT)Also known as the direct Coombs' test; this test is used to detect

antibodies or complement proteins that are bound to the surface of red blood cells

Fibreoptic phototherapy Phototherapy given using a single light source that comprises a light

generator, a fibreoptic cable through which the light is carried and a flexible light pad, on which

the baby is placed or that is wrapped around the baby

Multiple phototherapy Phototherapy that is given using more than one light source

simultaneously; for example two or more conventional units, or a combination of conventional

and fibreoptic units


https://www.gov.uk/government/publications/reference-guide-to-consent-for-examination-or-treatment-second-editionhttps://www.gov.uk/government/publications/reference-guide-to-consent-for-examination-or-treatment-second-editionhttp://www.justice.gov.uk/protecting-the-vulnerable/mental-capacity-acthttp://www.wales.nhs.uk/consenthttp://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyandGuidance/DH_4007005http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyandGuidance/DH_4007005http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyandGuidance/DH_4007005http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyandGuidance/DH_4007005http://www.wales.nhs.uk/consenthttp://www.justice.gov.uk/protecting-the-vulnerable/mental-capacity-acthttps://www.gov.uk/government/publications/reference-guide-to-consent-for-examination-or-treatment-second-editionhttps://www.gov.uk/government/publications/reference-guide-to-consent-for-examination-or-treatment-second-edition

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Near-term 35 to 36 weeks gestational age

Preterm Less than 37 weeks gestational age

Prolonged jaundice Jaundice lasting more than 14 days in term babies and more than 21 days

in preterm babies

Significant hyperbilirubinaemiaAn elevation of the serum bilirubin to a level requiring

treatment

Term 37 weeks or more gestational age

Visible jaundice Jaundice detected by visual inspection

Families and carers should also be given the information and support they need.



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Key priorities for implementation

Information

Offer parents or carers information about neonatal jaundice that is tailored to their needs and

expressed concerns. This information should be provided through verbal discussion backed

up by written information. Care should be taken to avoid causing unnecessary anxiety to

parents or carers. Information should include:

factors that influence the development of significant hyperbilirubinaemia

how to check the baby for jaundice

what to do if they suspect jaundice

the importance of recognising jaundice in the first 24 hours and of seeking urgent

medical advice

the importance of checking the baby's nappies for dark urine or pale chalky stools

the fact that neonatal jaundice is common, and reassurance that it is usually transient

and harmless

reassurance that breastfeeding can usually continue.

Care for all babies

Identify babies as being more likely to develop significant hyperbilirubinaemia if they have

any of the following factors:

gestational age under 38 weeks

a previous sibling with neonatal jaundice requiring phototherapy

mother's intention to breastfeed exclusively

visible jaundice in the first 24 hours of life.

In all babies:



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check whether there are factors associated with an increased likelihood of developing

significant hyperbilirubinaemia soon after birth

examine the baby for jaundice at every opportunity especially in the first 72 hours.

When looking for jaundice (visual inspection):

check the naked baby in bright and preferably natural light

examination of the sclerae, gums and blanched skin is useful across all skin tones.

Additional care

Ensure babies with factors associated with an increased likelihood of developing significant

hyperbilirubinaemia receive an additional visual inspection by a healthcare professional

during the first 48 hours of life.

Measuring bilirubin in all babies with jaundice

Do not rely on visual inspection alone to estimate the bilirubin level in a baby with jaundice.

How to measure the bilirubin level

When measuring the bilirubin level:

use a transcutaneous bilirubinometer in babies with a gestational age of 35 weeks or

more and postnatal age of more than 24 hours

if a transcutaneous bilirubinometer is not available, measure the serum bilirubin

if a transcutaneous bilirubinometer measurement indicates a bilirubin level greater

than 250 micromol/litre check the result by measuring the serum bilirubin

always use serum bilirubin measurement to determine the bilirubin level in babies with

jaundice in the first 24 hours of life

always use serum bilirubin measurement to determine the bilirubin level in babies less

than 35 weeks gestational age

always use serum bilirubin measurement for babies at or above the relevant treatment

threshold for their postnatal age, and for all subsequent measurements



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do not use an icterometer.

How to manage hyperbilirubinaemia

Use the bilirubin level to determine the management of hyperbilirubinaemia in all babies (see

threshold table[1] and treatment threshold graphs[2]).

Care of babies with prolonged jaundice

Follow expert advice about care for babies with a conjugated bilirubin level greater than 25

micromol/litre because this may indicate serious liver disease.

[1] The threshold table is in the 'Guidance' section of this guideline

[2] The treatment threshold graphs are in appendix D of the full guideline.



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1 Guidance

The following guidance is based on the best available evidence. The full guideline gives details

of the methods and the evidence used to develop the guidance.

Threshold table. Consensus-based bilirubin thresholds for management of babies 38

weeks or more gestational age with hyperbilirubinaemia

Age

(hours)

Bilirubin measurement (micromol/litre)

0 > 100 > 100

6 > 100 > 112 > 125 > 150

12 > 100 > 125 > 150 > 200

18 > 100 > 137 > 175 > 250

24 > 100 > 150 > 200 > 300

30 > 112 > 162 > 212 > 350

36 > 125 > 175 > 225 > 400

42 > 137 > 187 > 237 > 450

48 > 150 > 200 > 250 > 450

54 > 162 > 212 > 262 > 450

60 > 175 > 225 > 275 > 450

66 > 187 > 237 > 287 > 450

72 > 200 > 250 > 300 > 450

78 > 262 > 312 > 450

84 > 275 > 325 > 450

90 > 287 > 337 > 450

96+ > 300 > 350 > 450


http://guidance.nice.org.uk/CG98/Guidancehttp://guidance.nice.org.uk/CG98/Guidance

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Action Repeat

bilirubin

measurement

in

612 hours

Consider

phototherapy

and repeat

bilirubin

measurement in

6 hours

Start

phototherapy

Perform an exchange

transfusion unless the

bilirubin level falls below

threshold while the treatment

is being prepared

1.1 Information for parents or carers

1.1.1 Offer parents or carers information about neonatal jaundice that is tailored to

their needs and expressed concerns. This information should be provided

through verbal discussion backed up by written information. Care should be

taken to avoid causing unnecessary anxiety to parents or carers. Information

should include:

factors that influence the development of significant hyperbilirubinaemia

how to check the baby for jaundice

what to do if they suspect jaundice

the importance of recognising jaundice in the first 24 hours and of seeking urgent

medical advice

the importance of checking the baby's nappies for dark urine or pale chalky stools

the fact that neonatal jaundice is common, and reassurance that it is usually

transient and harmless

reassurance that breastfeeding can usually continue.

1.2 Care for all babies

1.2.1 Identify babies as being more likely to develop significant hyperbilirubinaemia if

they have any of the following factors:

gestational age under 38 weeks



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a previous sibling with neonatal jaundice requiring phototherapy

mother's intention to breastfeed exclusively

visible jaundice in the first 24 hours of life.

1.2.2 Ensure that adequate support is offered to all women who intend to breastfeed

exclusively[3].

1.2.3 In all babies:

check whether there are factors associated with an increased likelihood of

developing significant hyperbilirubinaemia soon after birth

examine the baby for jaundice at every opportunity especially in the first 72 hours.

1.2.4 Parents, carers and healthcare professionals should all look for jaundice

(visual inspection).

1.2.5 When looking for jaundice (visual inspection):

check the naked baby in bright and preferably natural light

examination of the sclerae, gums and blanched skin is useful across all skin tones.

1.2.6 Do not rely on visual inspection alone to estimate the bilirubin level in a baby

with jaundice.

1.2.7 Do not measure bilirubin levels routinely in babies who are not visibly

jaundiced.

1.2.8 Do not use any of the following to predict significant hyperbilirubinaemia:

umbilical cord blood bilirubin level

end-tidal carbon monoxide (ETCOc) measurement

umbilical cord blood direct antiglobulin test (DAT) (Coombs' test).

Additional care



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1.2.9 Ensure babies with factors associated with an increased likelihood of

developing significant hyperbilirubinaemia receive an additional visual

inspection by a healthcare professional during the first 48 hours of life.

Urgent additional care for babies with visible jaundice in the first 24 hours

1.2.10 Measure and record the serum bilirubin level urgently (within 2 hours) in all

babies with suspected or obvious jaundice in the first 24 hours of life.

1.2.11 Continue to measure the serum bilirubin level every 6 hours for all babies with

suspected or obvious jaundice in the first 24 hours of life until the level is both:

below the treatment threshold

stable and/or falling.

1.2.12 Arrange a referral to ensure that an urgent medical review is conducted (as

soon as possible and within 6 hours) for babies with suspected or obvious

jaundice in the first 24 hours of life to exclude pathological causes of jaundice.

1.2.13 Interpret bilirubin levels according to the baby's postnatal age in hours andmanage hyperbilirubinaemia according to the threshold table and treatment

threshold graphs[4].

Care for babies more than 24 hours old

1.2.14 Measure and record the bilirubin level urgently (within 6 hours) in all babies

more than 24 hours old with suspected or obvious jaundice.

How to measure the bilirubin level

1.2.15 When measuring the bilirubin level:

use a transcutaneous bilirubinometer in babies with a gestational age of 35 weeks

or more and postnatal age of more than 24 hours

if a transcutaneous bilirubinometer is not available, measure the serum bilirubin



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if a transcutaneous bilirubinometer measurement indicates a bilirubin level greater

than 250 micromol/litre check the result by measuring the serum bilirubin

always use serum bilirubin measurement to determine the bilirubin level in babieswith jaundice in the first 24 hours of life

always use serum bilirubin measurement to determine the bilirubin level in babies

less than 35 weeks gestational age

always use serum bilirubin measurement for babies at or above the relevant

treatment thresholds for their postnatal age, and for all subsequent measurements

do not use an icterometer.

1.3 Management and treatment of hyperbilirubinaemia

Information for parents or carers on treatment

1.3.1 Offer parents or carers information about treatment for hyperbilirubinaemia,

including:

anticipated duration of treatment

reassurance that breastfeeding, nappy-changing and cuddles can usually continue.

1.3.2 Encourage mothers of breastfed babies with jaundice to breastfeed frequently,

and to wake the baby for feeds if necessary.

1.3.3 Provide lactation/feeding support to breastfeeding mothers whose baby is

visibly jaundiced.

How to manage hyperbilirubinaemia

1.3.4 Use the bilirubin level to determine the management of hyperbilirubinaemia in

all babies (see threshold table and treatment threshold graphs[4]).

1.3.5 Do not use the albumin/bilirubin ratio when making decisions about the

management of hyperbilirubinaemia.



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1.4.6 Stop phototherapy once serum bilirubin has fallen to a level at least 50

micromol/litre below the phototherapy threshold (see threshold table and

treatment threshold graphs[4]).

1.4.7 Check for rebound of significant hyperbilirubinaemia with a repeat serum

bilirubin measurement 1218 hours after stopping phototherapy. Babies do not

necessarily have to remain in hospital for this to be done.

Type of phototherapy to use

1.4.8 Do not use sunlight as treatment for hyperbilirubinaemia.

Single phototherapy treatment for term babies

1.4.9 Use conventional 'blue light' phototherapy as treatment for significant

hyperbilirubinaemia in babies with a gestational age of 37 weeks or more

unless:

the serum bilirubin levels are rising rapidly (more than 8.5 micromol/litre per hour)

the serum bilirubin is at a level that is within 50 micromol/litre below the threshold for

which exchange transfusion is indicated after 72 hours (see the threshold table and


1.4.10 Do not use fibreoptic phototherapy as first-line treatment for

hyperbilirubinaemia for babies with a gestational age 37 weeks or more.

Single phototherapy treatment in preterm babies

1.4.11 Use either fibreoptic phototherapy or conventional 'blue light' phototherapy as

treatment for significant hyperbilirubinaemia in babies less than 37 weeks

unless:

the serum bilirubin levels are rising rapidly (more than 8.5 micromol/litre per hour)



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the serum bilirubin is at a level that is within 50 micromol/litre below the threshold for

which exchange transfusion is indicated after 72 hours (see threshold table and


Continuous multiple phototherapy treatment for term and preterm babies

1.4.12 Initiate continuous multiple phototherapy to treat all babies if any of the

following apply:

the serum bilirubin level is rising rapidly (more than 8.5 micromol/litre per hour)

the serum bilirubin is at a level within 50 micromol/litre below the threshold for which

exchange transfusion is indicated after 72 hours (see threshold table and treatment

threshold graphs[4]).

the bilirubin level fails to respond to single phototherapy (that is, the level of serum

bilirubin continues to rise, or does not fall, within 6 hours of starting single

phototherapy).

1.4.13 If the serum bilirubin level falls during continuous multiple phototherapy to a

level 50 micromol/litre below the threshold for which exchange transfusion is

indicated step down to single phototherapy.

Information for parents or carers on phototherapy

1.4.14 Offer parents or carers verbal and written information on phototherapy

including all of the following:

why phototherapy is being considered

why phototherapy may be needed to treat significant hyperbilirubinaemia

the possible adverse effects of phototherapy

the need for eye protection and routine eye care

reassurance that short breaks for feeding, nappy changing and cuddles will be

encouraged



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what might happen if phototherapy fails

rebound jaundice

potential long-term adverse effects of phototherapy

potential impact on breastfeeding and how to minimise this.

General care of the baby during phototherapy

1.4.15 During phototherapy:

place the baby in a supine position unless other clinical conditions prevent this

ensure treatment is applied to the maximum area of skin

monitor the baby's temperature and ensure the baby is kept in an environment that

will minimise energy expenditure (thermoneutral environment)

monitor hydration by daily weighing of the baby and assessing wet nappies

support parents and carers and encourage them to interact with the baby.

1.4.16 Give the baby eye protection and routine eye care during phototherapy.

1.4.17 Use tinted headboxes as an alternative to eye protection in babies with a

gestational age of 37 weeks or more undergoing conventional 'blue light'

phototherapy.

Monitoring the baby during phototherapy

1.4.18 During conventional 'blue light' phototherapy:

using clinical judgement, encourage short breaks (of up to 30 minutes) for

breastfeeding, nappy changing and cuddles

continue lactation/feeding support

do not give additional fluids or feeds routinely.



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Maternal expressed milk is the additional feed of choice if available, and when additional feeds

are indicated.

1.4.19 During multiple phototherapy:

do not interrupt phototherapy for feeding but continue administering intravenous/

enteral feeds

continue lactation/feeding support so that breastfeeding can start again when

treatment stops.

Maternal expressed milk is the additional feed of choice if available, and when

additional feeds are indicated.

Phototherapy equipment

1.4.20 Ensure all phototherapy equipment is maintained and used according to the

manufacturers' guidelines.

1.4.21 Use incubators or bassinets according to clinical need and availability.

1.4.22 Do not use white curtains routinely with phototherapy as they may impair

observation of the baby.

1.5 Factors that influence the risk of kernicterus

1.5.1 Identify babies with hyperbilirubinaemia as being at increased risk of

developing kernicterus if they have any of the following:

a serum bilirubin level greater than 340 micromol/litre in babies with a gestational

age of 37 weeks or more

a rapidly rising bilirubin level of greater than 8.5 micromol/litre per hour

clinical features of acute bilirubin encephalopathy.



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1.6 Formal assessment for underlying disease

1.6.1 In addition to a full clinical examination by a suitably trained healthcare

professional, carry out all of the following tests in babies with significant

hyperbilirubinaemia as part of an assessment for underlying disease (see

threshold table and treatment threshold graphs[4]):

serum bilirubin (for baseline level to assess response to treatment)

blood packed cell volume

blood group (mother and baby)

DAT (Coombs' test). Interpret the result taking account of the strength of reaction,

and whether mother received prophylactic anti-D immunoglobulin during pregnancy.

1.6.2 When assessing the baby for underlying disease, consider whether the

following tests are clinically indicated:

full blood count and examination of blood film

blood glucose-6-phosphate dehydrogenase levels, taking account of ethnic origin

microbiological cultures of blood, urine and/or cerebrospinal fluid (if infection is

suspected).

1.7 Care of babies with prolonged jaundice

1.7.1 In babies with a gestational age of 37 weeks or more with jaundice lasting

more than 14 days, and in babies with a gestational age of less than 37 weeks

and jaundice lasting more than 21 days:

look for pale chalky stools and/or dark urine that stains the nappy

measure the conjugated bilirubin

carry out a full blood count



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carry out a blood group determination (mother and baby) and DAT (Coombs' test).

Interpret the result taking account of the strength of reaction, and whether mother

received prophylactic anti-D immunoglobulin during pregnancy.

carry out a urine culture

ensure that routine metabolic screening (including screening for congenital

hypothyroidism) has been performed.

1.7.2 Follow expert advice about care for babies with a conjugated bilirubin level

greater than 25 micromol/litre because this may indicate serious liver disease.

1.8 Intravenous immunoglobulin

1.8.1 Use intravenous immunoglobulin (IVIG) (500 mg/kg over 4 hours) as an

adjunct to continuous multiple phototherapy in cases of Rhesus haemolytic

disease or ABO haemolytic disease when the serum bilirubin continues to rise

by more than 8.5 micromol/litre per hour.

1.8.2 Offer parents or carers information on IVIG including:

why IVIG is being considered

why IVIG may be needed to treat significant hyperbilirubinaemia

the possible adverse effects of IVIG

when it will be possible for parents or carers to see and hold the baby.

1.9 Exchange transfusion1.9.1 Offer parents or carers information on exchange transfusion including:

the fact that exchange transfusion requires that the baby be admitted to an intensive

care bed

why an exchange transfusion is being considered

why an exchange transfusion may be needed to treat significant hyperbilirubinaemia



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the possible adverse effects of exchange transfusions

when it will be possible for parents or carers to see and hold the baby after the

exchange transfusion.

1.9.2 Use a double-volume exchange transfusion to treat babies:

whose serum bilirubin level indicates its necessity (see threshold table and

treatment threshold graphs[4]) and/or

with clinical features and signs of acute bilirubin encephalopathy.

1.9.3 During exchange transfusion do not :

stop continuous multiple phototherapy

perform a single-volume exchange

use albumin priming

routinely administer intravenous calcium.

1.9.4 Following exchange transfusion:

maintain continuous multiple phototherapy

measure serum bilirubin level within 2 hours and manage according to the threshold

table and treatment threshold graphs[4].

1.10 Other therapies

1.10.1 Do not use any of the following to treat hyperbilirubinaemia:

agar

albumin

barbiturates

charcoal



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cholestyramine

clofibrate

D-penicillamine

glycerin

manna

metalloporphyrins

riboflavin

traditional Chinese medicine

acupuncture

homeopathy.

[3] Refer to Routine postnatal care of women and their babies (NICE clinical guideline 37) for

information on breastfeeding support.

[4] The treatment threshold graphs are in appendix D of the full guideline.


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2 Notes on the scope of the guidance

NICE guidelines are developed in accordance with a scope that defines what the guideline will

and will not cover. The scope of this guideline is available.

This guideline covers all babies with jaundice from birth up to 28 days of age. Special attention

was given to the recognition and management of neonatal jaundice in babies with dark skin

tones.

It does not cover babies with jaundice that lasts beyond the first 28 days of life, babies with

jaundice that requires surgical treatment to correct the underlying cause and babies with

conjugated hyperbilirubinaemia.

How this guideline was developed

NICE commissioned the National Collaborating Centre for Women's and Children's Health to

develop this guideline. The Centre established a guideline development group (see appendix A),

which reviewed the evidence and developed the recommendations. An independent guideline

review panel oversaw the development of the guideline (see appendix B).

There is more information about how NICE clinical guidelines are developed on the NICE

website. See also NICE's How NICE clinical guidelines are developed: an overview for

stakeholders, the public and the NHS.


http://guidance.nice.org.uk/CG/Wave14/82/Scopehttp://www.nice.org.uk/HowWeWorkhttp://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp?domedia=1&mid=62F02D9B-19B9-E0B5-D4A26EC9A934FDC7http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp?domedia=1&mid=62F02D9B-19B9-E0B5-D4A26EC9A934FDC7http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp?domedia=1&mid=62F02D9B-19B9-E0B5-D4A26EC9A934FDC7http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp?domedia=1&mid=62F02D9B-19B9-E0B5-D4A26EC9A934FDC7http://www.nice.org.uk/HowWeWorkhttp://guidance.nice.org.uk/CG/Wave14/82/Scope

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3 Implementation

NICE has developed tools to help organisations implement this guidance.


http://guidance.nice.org.uk/CG98http://guidance.nice.org.uk/CG98

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4 Research recommendations

The Guideline Development Group has made the following recommendations for research,

based on its review of evidence, to improve NICE guidance and patient care in the future. The

Guideline Development Group's full set of research recommendations is detailed in the full

guideline (see section 5).

4.1 Breastfeeding and hyperbilirubinaemia

What are the factors that underlie the association between breastfeeding and jaundice?

Why this is important

Breastfeeding has been shown to be a factor in significant hyperbilirubinaemia. The reasons for

this association have not yet been fully elucidated.

This question should be answered by studying infants in the first 28 days of life receiving

different feeding types (breast milk, formula feeds or mixed feeds). Infants who do not develop

significant hyperbilirubinaemia should be compared with infants with significant

hyperbilirubinaemia. The outcomes chosen should include maternal factors, neonatal factors and

blood analyses.

4.2 Trancutaneous bilirubin screening and risk factors

What is the comparative effectiveness and cost-effectiveness of universal pre-discharge

transcutaneous bilirubin screening alone or combined with a risk assessment in reducing

jaundice-related neonatal morbidity and hospital readmission?


There is good evidence that a risk assessment that combines the result of a timed

transcutaneous bilirubin level with risk factors for significant hyperbilirubinaemia is effective at

preventing later significant hyperbilirubinaemia.

This question should be answered by studying the effects of timed pre-discharge transcutaneous

bilirubin levels and timed pre-discharge transcutaneous bilirubin levels combined with risk



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assessment. The study population should consist of babies in the first 28 days of life, with

subgroups including near-term babies and babies with dark skin tones. The interventions should

be compared with standard care (discharge without timed transcutaneous bilirubin level), and the

outcomes chosen should include significant hyperbilirubinaemia, cost-effectiveness and parental

anxiety.

4.3 Transcutaneous bilirubinometers

What is the comparative accuracy of the Minolta JM-103 and the BiliChek when compared to

serum bilirubin levels in all babies?


The accuracy of transcutaneous bilirubinometers (Minolta JM-103 and BiliChek) has been

adequately demonstrated in term babies below treatment levels (bilirubin less than

250 micromol/litre). New research is needed to evaluate the accuracy of different transcutaneous

bilirubinometers in comparison to serum bilirubin levels in all babies.

This question should be answered by comparing bilirubin levels taken using different

transcutaneous bilirubinometers with bilirubin levels assessed using serum (blood) tests. Thestudy population should comprise babies in the first 28 days of life, with subgroups including

preterm babies, babies with dark skin tones, babies with high levels of bilirubin and babies after

phototherapy. The outcomes chosen should include diagnostic accuracy (sensitivity, specificity,

positive predictive value, negative predictive value), parental anxiety, staff and parental

satisfaction with test and cost effectiveness.

4.4 Interruptions during phototherapy

How frequently and for how long can conventional phototherapy be interrupted without adversely

effecting clinical outcomes?


The effectiveness and tolerability of intermittent phototherapy has been adequately

demonstrated in term babies at low treatment levels (bilirubin less than 250 micromol/litre). New



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research is needed to evaluate the effectiveness and tolerability of different frequencies of

interruptions of different durations.

The study population should comprise babies in the first 28 days of life in conventional

phototherapy. Interruptions of 45 or 60 minutes would be made either on demand, every hour or

every 2 hours, and compared with interruptions of up to 30 minutes every 3 hours. The outcomes

chosen should include effectiveness in terms of the mean decrease in bilirubin levels and the

mean duration of phototherapy. Extra outcomes could include adverse effects, parental bonding

and parental anxiety, staff and parental satisfaction with treatment and cost effectiveness.

4.5 National registries

National registries are needed of cases of significant hyperbilirubinaemia, kernicterus and

exchange transfusions.


There is good evidence that prospective surveys in the UK and data from a national kernicterus

register in the US can help to identify root causes of kernicterus and acute bilirubin

encephalopathy.

The study population should comprise all children with a peak bilirubin level greater than

450 micromol/litre, which is the threshold for an exchange transfusion recommended by NICE.

The intervention would be maternal, prenatal, perinatal and neonatal factors. The outcomes

chosen should be shortcomings in clinical and service provision to prevent recurring themes in

kernicterus cases.



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5 Other versions of this guideline

5.1 Full guideline

The full guideline, Neonatal jaundice, contains details of the methods and evidence used to

develop the guideline. It is published by the National Collaborating Centre for Women's and

Children's Health, and is available from ourwebsite.

5.2 Quick reference guide

A quick reference guide for healthcare professionals is available.

5.3 Information for the public

NICE has produced information for the public explaining this guideline.

We encourage NHS and voluntary sector organisations to use text from this information in their

own materials.


http://guidance.nice.org.uk/CG98/guidancehttp://guidance.nice.org.uk/CG98/Guidance/pdf/Englishhttp://guidance.nice.org.uk/CG98/QuickRefGuide/pdf/Englishhttp://publications.nice.org.uk/IFP98http://publications.nice.org.uk/IFP98http://guidance.nice.org.uk/CG98/QuickRefGuide/pdf/Englishhttp://guidance.nice.org.uk/CG98/Guidance/pdf/Englishhttp://guidance.nice.org.uk/CG98/guidance

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6 Related NICE guidance

Published

Diabetes in pregnancy: management of diabetes and its complications from pre-conception

to the postnatal period. NICE clinical guideline 63 (2008).

Antenatal care: routine care for the healthy pregnant woman. NICE clinical guideline 62

(2008).

Intrapartum care: care of healthy women and their babies during childbirth. NICE clinical

guideline 55 (2007).

Routine postnatal care of women and their babies. NICE clinical guideline 37 (2006).


http://guidance.nice.org.uk/CG63http://guidance.nice.org.uk/CG63http://guidance.nice.org.uk/CG62http://guidance.nice.org.uk/CG55http://guidance.nice.org.uk/CG37http://guidance.nice.org.uk/CG37http://guidance.nice.org.uk/CG55http://guidance.nice.org.uk/CG62http://guidance.nice.org.uk/CG63http://guidance.nice.org.uk/CG63

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7 Updating the guideline

NICE clinical guidelines are updated so that recommendations take into account important new

information. New evidence is checked 3 years after publication, and healthcare professionals

and patients are asked for their views; we use this information to decide whether all or part of a

guideline needs updating. If important new evidence is published at other times, we may decide

to do a more rapid update of some recommendations. Please see our website for information

about updating the guideline.



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Appendix A: The Guideline Development Group and

acknowledgements

Janet Rennie

Consultant and Senior Lecturer in Neonatal Medicine, Elizabeth Garrett Anderson Institute for

Women's Health, University College London Hospitals NHS Foundation Trust

Christiana Aride

GP, Tynemouth Medical Practice, London

Jay Bannerjee (until Mar 09)

Clinical Co-director, National Collaborating Centre for Women's and Children's Health

Yvonne Benjamin

Community Midwife, Leicester Royal Infirmary

Shona Burman-Roy (from Sep 09)

Senior Research Fellow, National Collaborating Centre for Women's and Children's Health

Katherine Cullen

Health Economist, National Collaborating Centre for Women's and Children's Health

Hannah-Rose Douglas


Karen Ford

Senior Lecturer, De Montfort University, Leicester

Itrat Iqbal (until Aug 09)


Kevin Ives

Consultant Neonatologist, John Radcliffe Hospital, Oxford

Paul Jacklin




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Maria Jenkins

Parent member

Alison Johns

Transitional Care Sister, University College London Hospitals NHS Foundation Trust

Juliet Kenny (from Jan 10)

Project Manager, National Collaborating Centre for Women's and Children's Health

Rajesh Khanna (until Apr 09)

Senior Research Fellow, National Collaborating Centre for Women's and Children's Health

Rosalind Lai

Information Scientist, National Collaborating Centre for Women's and Children's Health

Donal Manning

Consultant Paediatrician, Wirral University Teaching Hospital NHS Foundation Trust

Hugh McGuire

Research Fellow, National Collaborating Centre for Women's and Children's Health

Stephen Murphy (from Sep 09)


Caroline Ortega (until Apr 09)

Work Programme Co-ordinator, National Collaborating Centre for Women's and Children's Health

Kristina Pedersen (until Oct 09)

Project Manager, National Collaborating Centre for Women's and Children's Health

Edmund Peston

Document Supply Coordinator

Debbie Pledge (until Apr 09)

Senior Information Scientist, National Collaborating Centre for Women's and Children's Health



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Farrah Pradhan

Parent member

Wendy Riches

Executive Director, National Collaborating Centre for Women's and Children's Health

Anuradha Sekhri

Freelance Systematic Reviewer

Debra Teasdale

Head of Department Health, Wellbeing and the Family, Canterbury Christ Church University

Martin Whittle (until September 09)


NICE project team

Christine Carson

Programme Director

Caroline Keir (until January 2010), Sue Latchem (from January 2010)

Guideline Commissioning Manager

Nick Staples (until January 2010), Elaine Clydesdale (from January 2010)

Guidelines Coordinator

Judith Thornton

Technical lead

Acknowledgements

The NCC-WCH and the Guideline Development Group (GDG) would like to thank Dr Giles

Kendall MBBS, BSc(hons), MRCPCH PhD, Academic Clinical Lecturer Neonatal Medicine,

University College London/University College London Hospital NHS Foundation Trust and TJ

Cole, Professor of Medical Statistics, MRC Centre of Epidemiology for Child Health, UCL



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Institute of Child Health for allowing the GDG to adapt their Excel spreadsheet in developing the

treatment threshold graphs included in this guideline.



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Appendix B: The Guideline Review Panel

The Guideline Review Panel is an independent panel that oversees the development of the

guideline and takes responsibility for monitoring adherence to NICE guideline development

processes. In particular, the panel ensures that stakeholder comments have been adequately

considered and responded to. The panel includes members from the following perspectives:

primary care, secondary care, lay, public health and industry.

Dr John Hyslop (Chair)

Consultant Radiologist, Royal Cornwall Hospital NHS Trust

Dr Ash Paul

Medical Director, Bedfordshire Primary Care Trust

Mr Peter Gosling

Lay member

Professor Liam Smeeth

Professor of Clinical Epidemiology, London School of Hygiene and Tropical Medicine

Mr Kieran Murphy

Health Economics and Reimbursement Manager, Johnson & Johnson Medical Devices &

Diagnostics, UK



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Appendix C: The algorithms

The quick reference guide contains algorithms on investigation, phototherapy and exchange

transfusion for babies with neonatal jaundice.


http://guidance.nice.org.uk/CG98/QuickRefGuide/pdf/Englishhttp://guidance.nice.org.uk/CG98/QuickRefGuide/pdf/English

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Appendix D: The treatment threshold graphs

The threshold graphs are available in the full guideline.


http://guidance.nice.org.uk/CG98/Guidance/pdf/Englishhttp://guidance.nice.org.uk/CG98/Guidance/pdf/English

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About this guideline

NICE clinical guidelines are recommendations about the treatment and care of people with

specific diseases and conditions in the NHS in England and Wales.

The guideline was developed by the National Collaborating Centre for Womens' and Children's

Health. The Collaborating Centre worked with a group of healthcare professionals (including

consultants, GPs and nurses), patients and carers, and technical staff, who reviewed the

evidence and drafted the recommendations. The recommendations were finalised after public

consultation.

The methods and processes for developing NICE clinical guidelines are described in The

guidelines manual.

The recommendations from this guideline have been incorporated into the neonatal jaundice and

postnatal care NICE Pathways. We have produced information for the public explaining this

guideline. Tools to help you put the guideline into practice and information about the evidence it

is based on are also available.

Changes after publication

July 2013: minor maintenance

January 2012: minor maintenance

Your responsibility

This guidance represents the view of NICE, which was arrived at after careful consideration ofthe evidence available. Healthcare professionals are expected to take it fully into account when

exercising their clinical judgement. However, the guidance does not override the individual

responsibility of healthcare professionals to make decisions appropriate to the circumstances of

the individual patient, in consultation with the patient and/or guardian or carer, and informed by

the summary of product characteristics of any drugs they are considering.

Implementation of this guidance is the responsibility of local commissioners and/or providers.

Commissioners and providers are reminded that it is their responsibility to implement the


http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguidelinedevelopmentmethods/clinical_guideline_development_methods.jsphttp://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguidelinedevelopmentmethods/clinical_guideline_development_methods.jsphttp://pathways.nice.org.uk/pathways/neonatal-jaundicehttp://pathways.nice.org.uk/pathways/postnatal-carehttp://publications.nice.org.uk/IFP98http://guidance.nice.org.uk/CG98http://guidance.nice.org.uk/CG98http://publications.nice.org.uk/IFP98http://pathways.nice.org.uk/pathways/postnatal-carehttp://pathways.nice.org.uk/pathways/neonatal-jaundicehttp://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguidelinedevelopmentmethods/clinical_guideline_development_methods.jsphttp://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/clinicalguidelinedevelopmentmethods/clinical_guideline_development_methods.jsp

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